In silico Therapeutics for Neurogenic Hypertension and Vasovagal Syncope.
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ABSTRACT:
SUBMITTER: Bojic T
PROVIDER: S-EPMC4720751 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Project description:Syncope, defined as a transient loss of consciousness caused by transient global cerebral hypoperfusion, affects 30-40% of humans during their lifetime. Vasovagal syncope (VVS) is the most common cause of syncope, the etiology of which is still unclear. This review summarizes data on the genetics of VVS, describing the inheritance pattern of the disorder, candidate gene association studies and genome-wide studies. According to this evidence, VVS is a complex disorder, which can be caused by the interplay between genetic factors, whose contribution varies from monogenic Mendelian inheritance to polygenic inherited predisposition, and external factors affecting the monogenic (resulting in incomplete penetrance) and polygenic syncope types.
| S-EPMC8508958 | biostudies-literature
Project description:BackgroundsVasovagal syncope (VVS) is a common form of syncope. In children with VVS, recurrent syncope or presyncope can affect the physical and mental health of both children and parents, which markedly impairs quality of life.ObjectivesWe aimed to identify factors at baseline that can predict the recurrence of syncope or presyncope over a 5-year follow-up period, and further to develop a prognostic nomogram model.MethodsThis cohort is bidirectional in design. From July 2017 to August 2022, children with VVS were included and followed up every 3 to 6 months. Head-up Tilt Test (HUTT) was performed for diagnosing VVS. Data were analyzed using STATA software, and risk estimates are presented as hazard ratio (HR) and 95% confidence interval (CI).ResultsTotal 352 children with VVS who had complete information were included in this study. Median follow-up time was 22 months. Overall, supine mean arterial pressure (MAP-supine) in HUTT and baseline urine specific gravity (USG) were associated with the significant risk of syncope or presyncope recurrence (HR: 0.70 and 3.00, respectively; both P < 0.05). Calibration and discrimination analyses revealed that the addition of MAP-supine and USG can result in a better fit. A prognostic nomogram model based on significant factors annexed with five traditional promising factors was finally constructed, with strong discriminative and predictive abilities (C-index approaching 0.700, P < 0.05).ConclusionsOur findings indicated that MAP-supine and USG can independently predict the significant risk of syncope recurrence in children with VVS, and the prediction was more obvious in a nomogram model.
| S-EPMC10031040 | biostudies-literature
Project description:Vasovagal syncope (VVS) is a chronic debilitating condition seen mostly in young women of reproductive age. There are anecdotal reports of increased syncope and presyncope around menstruation. This case-control study assessed the effects of the menstrual cycle on lightheadedness episodes and compared the gynecological and pregnancy history of VVS patients to healthy subjects.A custom-designed gynecological and menstrual cycle questionnaire was previously developed for patients with orthostatic intolerance. This questionnaire was administered to female patients with VVS (n = 128) as a part of the multicenter Second Prevention of Syncope Trial, and to gender-matched healthy subjects (n = 92).VVS patients and healthy subjects reported significant variability in self-reported lightheadedness throughout the menstrual cycle. Both cohorts experienced greatest lightheadedness during menses (53 ± 2 vs. 56 ± 4), which decreased during the follicular phase (44 ± 2 vs. 41 ± 4). VVS patients reported less severity in premenstrual symptoms (Fisher's method P = 2.7E-06) compared to healthy controls. There is no difference in the incidence of gynecological abnormalities (Fisher's exact P = 0.193) and pregnancy complications (P = 1.0) between the two cohorts. VVS patients have similar pregnancy rates compared to healthy subjects (P = 0.674).The severity of lightheadedness varies during the menstrual cycle and is similar in both VVS patients and healthy controls. VVS patients have no greater risk of gynecological abnormalities and pregnancy complications than healthy subjects.
| S-EPMC3681885 | biostudies-literature
Project description:PurposeThe study was designed to investigate the profile of plasma human growth cytokines in pediatric vasovagal syncope (VVS).Materials and methodsIn the discovery set of the study, plasma human growth cytokines were measured using a Quantiboby Human Growth Factor Array in 24 VVS children and 12 healthy controls. Scatter and principal component analysis (PCA) diagrams were used to describe the samples, an unsupervised hierarchical clustering analysis was used to categorize the samples. Subsequently, the cytokines obtained from the screening assays were verified with a suspension cytokine array in the validation set of the study including 53 VVS children and 24 controls. Finally, the factors associated with pediatric VVS and the predictive value for the diagnosis of VVS were determined.ResultsIn the discovery study, the differential protein screening revealed that the plasma hepatocyte growth factor (HGF), transforming growth factor b1 (TGF-b1), insulin-like growth factor binding protein (IGFBP)-4, and IGFBP-1 in children suffering from VVS were higher than those of the controls (all adjust P- value < 0.05). However, the plasma IGFBP-6, epidermal growth factor (EGF), and IGFBP-3 in pediatric VVS were lower than those of the controls (all adjust P- value < 0.01). Meanwhile, the changes of 7 differential proteins were analyzed by volcano plot. Unsupervised hierarchical cluster analysis demonstrated that patients in the VVS group could be successfully distinguished from controls based on the plasma level of seven differential proteins. Further validation experiments showed that VVS patients had significantly higher plasma concentrations of HGF, IGFBP-1, and IGFBP-6, but lower plasma concentrations of EGF and IGFBP-3 than controls. The logistics regression model showed that increased plasma concentration of HGF and IGFBP-1 and decreased plasma concentration of EGF were correlated with the development of pediatric VVS. ROC curve analysis showed that the abovementioned 3 proteins were useful for assisting the diagnosis of VVS.ConclusionPlasma human growth cytokine profiling changed in pediatric VVS. Elevated plasma concentrations of HGF and IGFBP-1, and decreased EGF were associated factors in the development of pediatric VVS. The abovementioned three proteins are helpful for the diagnosis of pediatric VVS.
| S-EPMC9614254 | biostudies-literature
Project description:This clinical case report presents synchronous physiological data from an individual in whom a spontaneous vasovagal reaction occurred without syncope. The physiological data are presented for three main phases: Baseline (0-200 s), vasovagal reaction (200-600 s), and recovery period (600-1200 s). The first physiological changes occurred at around 200 s, with a decrease in blood pressure, peak in heart rate and vastus lateralis tissue oxygenation, and a drop in alpha power. The vasovagal reaction was associated with a progressive decrease in blood pressure, heart rate and cerebral oxygenation, whilst the mean middle cerebral artery blood flow velocity and blood oxygen saturation remained unchanged. Heart rate variability parameters indicated significant parasympathetic activation with a decrease in sympathetic tone and increased baroreflex sensitivity. The total blood volume and tissue oxygenation index (TOI) dropped in the brain but slightly increased in the vastus lateralis, suggesting cerebral hypoperfusion with blood volume pooling in the lower body part. Cerebral hypoperfusion during the vasovagal reaction was associated with electroencephalography (EEG) flattening (i.e., decreased power in beta and theta activity) followed by an EEG high-amplitude "slow" phase (i.e., increased power in theta activity). The subject developed signs and symptoms of pre-syncope with EEG flattening and slowing during prolonged periods of symptomatic hypotension, but did not lose consciousness.
| S-EPMC6914691 | biostudies-literature
Project description:ObjectiveTo describe the combination of tilt-induced vasovagal syncope (VVS) and psychogenic pseudosyncope (PPS) and aid its clinical recognition.MethodsWe identified people with tilt-induced VVS/PPS from 2 tertiary syncope referral centers. For each case, 3 controls with tilt-induced VVS were selected at random from the same center. Clinical characteristics were compared between both groups adjusting for multiple comparisons.ResultsOf 1,164 tilt-table tests, 23 (2%) resulted in VVS/PPS; these 23 cases were compared with 69 VVS controls. VVS and PPS coincided more often than chance would predict: 2% vs 0.6%, p < 0.001. Typical VVS prodromes and triggers were reported in all people with VVS/PPS and in controls with VVS. Attack frequency was significantly higher in the VVS/PPS (2 per month, range 0.1-60) than in the VVS group (0.25 per month, range 0.02-4; p < 0.001). Delayed recovery of consciousness was more frequently reported in the VVS/PPS group (likelihood ratio [+LR] 8.14, 95% confidence interval [CI] 3.94-16.84), as well as episodes without prodromes (+LR 5.57, 95% CI 2.53-12.26), atypical triggers (+LR 5.00, 95% CI 2.04-12.24), eye closure (+LR 3.75, 95% CI 1.68-8.35), and apparent loss of consciousness >1 minute (+LR 2.86, 95% CI 1.98-4.13).ConclusionsVVS/PPS presents with a complex phenotype. High attack frequency, delayed recovery of consciousness, apparent loss of consciousness >1 minute, ictal eye closure, atypical triggers, and the absence of prodromes may serve as indicators that PPS coincides with VVS.
| S-EPMC4676758 | biostudies-literature
Project description:Background Recent research has revealed that vasovagal syncope (VVS) leads to a high incidence of injuries; however, clinical associations of injury are not well-established. We present data from an ongoing VVS cohort and aimed to determine characteristics associated with VVS-related injury. Methods and Results Between 2017 and 2020, consecutive patients ≥18 years of age presenting to a tertiary syncope unit and diagnosed with VVS were included. Clinical characteristics relevant to syncope were obtained for the index episode. The outcome was incidence of injury during VVS, documented by clinical evaluation at the syncope clinic. Among 1115 patients (mean age, 45.9 years; 48% women), 260 injuries (23%) occurred. History of VVS-related injuries (adjusted relative risk [aRR], 1.80 [95% CI, 1.42-2.29]), standing position (aRR, 1.34 [95% CI, 1.06-1.68]), and female sex (aRR, 1.30 [95% CI, 1.06-1.60]) were associated with injury, whereas recurrent VVS (aRR, 0.63 [95% CI, 0.49-0.81]) and syncope in the noon/afternoon (aRR, 0.70 [95% CI, 0.56-0.87]) and evening/night (aRR, 0.43 [95% CI, 0.33-0.57]) compared with morning hours were associated with lower risk. There was a trend for higher rates of injury with overweight/obesity (aRR, 1.23 [95% CI, 0.99-1.54]) and syncope occurring at home (aRR, 1.22 [95% CI, 0.98-1.51]). In a per-syncope analysis considering up to 3 previous episodes (n=2518, 36% traumatic), syncope at home (aRR, 1.33 [95% CI, 1.17-1.51]) and absence of prodromes (aRR, 1.34 [95% CI, 1.09-1.61]) were associated with injury. Conclusions Patient characteristics, VVS presentations, the circumstances, and surroundings can determine the risk of injury. These associations of VVS-related injury identify at-risk individuals and high-risk situations. Future prospective studies are needed to investigate potential strategies for prevention of post-VVS injury in recurrent cases.
| S-EPMC9973565 | biostudies-literature
Project description:Objective: We aimed to establish useful models for the clinical differential diagnosis between vasovagal syncope (VVS) and psychogenic pseudosyncope (PPS). Methods: This bicentric study included 176 patients (150 VVS and 26 PPS cases) for model development. Based on the results of univariate and multivariate analyses, a logistic regression model and a scoring model were established and their abilities to differentiate VVS from PPS were tested. Another 78 patients (53 VVS and 25 PPS) were used for external validation. Results: In the logistic regression model, the outcome indicated that the QT-dispersion (QTd) (P < 0.001), syncope duration (P < 0.001), and upright posture (P < 0.001) acted as independent factors for the differentiation of VVS from PPS, which generated an area under the curve (AUC) of 0.892. A cutoff value of 0.234 yielded a sensitivity and specificity of 89.3 and 80.8%, respectively, for the differentiation between VVS and PPS in the logistic regression model. In the scoring model which consists of three variables, a cutoff score of three points yielded a sensitivity and specificity of 91.3 and 76.9%, respectively, with an AUC of 0.909. The external validation test indicated that the negative and positive predictive values of the scoring model were 78.8 and 91.7%, respectively, and the accuracy was 80.8%. Conclusion: The scoring model consisting of three variables is an easy-to-perform, inexpensive, and non-invasive measure for initial differential diagnosis between VVS and PPS.
| S-EPMC6989585 | biostudies-literature
Project description:Vasovagal Syncope (VVS) can lead to a markedly diminished quality of life for some patients. While there are many treatments for this condition including physical, mechanical, pharmacologic, and device-based control of heart rate, there are few that have been shown to be effective in randomized clinical trials. In our local experience, we have achieved significant improvement in symptom frequency and quality of life using algorithms based on the data available and on clinical acumen for the majority of patients with VVS. Despite this, there are still many patients who suffer from treatment refractory VVS. Fortunately, there are a number of ongoing clinical trials that are likely to add to our knowledge. Ongoing clinical trials are reviewed to examine new treatment methods for VVS that were listed on public trial registries as of April 15, 2014. Data from these trials should inform future strategies in the care of patients with VVS.
| S-EPMC4139437 | biostudies-literature
Project description:OBJECTIVE:Syncope is sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). We previously demonstrated impaired post-synaptic adrenergic responsiveness in young VVS patients was reversed by blocking nitric oxide synthase (NOS). We hypothesised that nitric oxide may account for reduced orthostatic tolerance in young recurrent VVS patients. METHODS:We recorded haemodynamics in supine VVS and healthy volunteers (aged 15-27 years), challenged with graded lower body negative pressure (LBNP) (-15, -30, -45?mm Hg each for 5?min, then -60?mm Hg for a maximum of 50?min) with and without NOS inhibitor NG-monomethyl-L-arginine acetate (L-NMMA). Saline plus phenylephrine (Saline+PE) was used as volume and pressor control for L-NMMA. RESULTS:Controls endured 25.9±4.0?min of LBNP during Saline+PE compared with 11.6±1.4?min for fainters (p<0.001). After L-NMMA, control subjects endured 24.8±3.2?min compared with 22.6±1.6?min for fainters. Mean arterial pressure decreased more in VVS patients during LBNP with Saline+PE (p<0.001) which was reversed by L-NMMA; cardiac output decreased similarly in controls and VVS patients and was unaffected by L-NMMA. Total peripheral resistance increased for controls but decreased for VVS during Saline+PE (p<0.001) but was similar following L-NMMA. Splanchnic vascular resistance increased during LBNP in controls, but decreased in VVS patients following Saline+PE which L-NMMA restored. CONCLUSIONS:We conclude that arterial vasoconstriction is impaired in young VVS patients, which is corrected by NOS inhibition. The data suggest that both pre- and post-synaptic arterial vasoconstriction may be affected by nitric oxide.
| S-EPMC5819615 | biostudies-literature